In the early months of 2020, as pediatric IBD centers across five countries adjusted to the realities of a global pandemic, a quiet but important effort was underway.
Early Data Support New Option
At 19 sites, clinicians were enrolling a group of children with moderate to severe active ulcerative colitis who had burned through corticosteroids, immunomodulators, biologics, or JAK inhibitors, often with disappointing durability. Many had already cycled through anti-TNF therapy, a mainstay with well-known limitations in the pediatric setting. It was in this context that SHINE-1 began: a phase 2, open-label, multicenter exploration of a new IL-23p19 inhibitor, mirikizumab, now tested in children aged 2–17 years.
“Currently, anti-TNF agents are the only FDA approved biologic/advanced therapy for children with moderate to severe UC,” the study’s first author, Jess L. Kaplan, MD, of the Division of Pediatric Gastroenterology and Nutrition at Mass General for Children, Boston, told GI & Hepatology News. “While anti-TNF therapy is effective for many children, it is not effective for all children and many children who initially respond will lose response over time. This is the first published clinical trial data on IL-23 inhibitors in children with UC and shows mirikizumab to be safe and effective for this population.”
For the trial, published in The Lancet Gastroenterology & Hepatology, Dr. Kaplan and colleagues enrolled 26 enrolled of 49 children screened. All received weight based IV induction at weeks 0, 4, and 8, followed by subcutaneous maintenance every 4 weeks through week 52. Non-responders at week 12 received a second 12-week induction.
Trial Results
By week 12, nearly 70% achieved clinical response and about 39% were in clinical remission by modified Mayo score. Endoscopic remission—arguably the most reassuring marker for long-term outcomes in UC—was seen in 54% of study participants, while symptomatic remission occurred in 46%. Pediatric Ulcerative Colitis Activity Index results paralleled these findings; 77% responded and 39% achieved remission by week 12.
By week 52, 54% of study participants maintained clinical response, 38.5% remained in clinical remission and 38.5% were in endoscopic remission. Notably, 38.5% achieved corticosteroid-free remission for at least 12 weeks leading to week 52.
“I was pleasantly surprised at the relatively high modified Mayo score clinical response rate after induction in a treatment refractory population where 65% of patients were previously biologic exposed,” Dr. Kaplan said. “I was also surprised by the relatively high rate of sustained response out to week 52 in week 12 responders and by the relatively high endoscopic remission at week 12.”
Endoscopic healing improved over time, with histologic-endoscopic mucosal remission rising from a single patient at week 12 to nine patients (34.6%) by week 52.
Safety and Limitations
In the realm of safety, no deaths occurred, and only three serious adverse events were reported: non-infective appendicitis, pseudarthrosis, and worsening UC (the latter leading to the single treatment discontinuation). The most common adverse events were benign and familiar: injection-site pain, headache, fever, and viral URIs. No opportunistic infections, malignancies, or thromboembolic events were reported during the study period. Growth parameters improved steadily in participants who weighed 40 kg or less.
The researchers cited the study’s small sample size and lack of randomization as key limitations. They explained that including a placebo or direct comparator group was not feasible or ethically appropriate in pediatric inflammatory bowel disease research.
“The results of this study indicate that mirikizumab therapy in pediatric patients with ulcerative colitis resulted in clinical improvement as assessed using multiple disease activity measures,” the authors concluded. “Subgroup analyses also suggest that mirikizumab showed efficacy in participants with a history of failed response to previous biological therapies, suggesting its potential as a treatment option in refractory cases.”
Real-World Evidence Needed
In an accompanying editorial, Stephanie A. Vuijk, Esmée H. Boute, and Lissy de Ridder, PhD, from the Department of Pediatric Gastroenterology at Erasmus Medical Center in Rotterdam, the Netherlands, wrote that they agreed with the researchers’ decision not to include a placebo or other comparator arm in the study, citing ethical and feasibility constraints. “However, assessing whether mirikizumab is more effective and safer than agents such as anti-TNFs or ustekinumab remain important,” they noted. “Head-to-head or randomized controlled trials would offer valuable insights but would be difficult to do because there is a relatively small pool of pediatric patients with ulcerative colitis on biologicals from which to select. Real-world data, including safety registries, should be taken into account to gain more information on safety and efficacy and speed up authorization of new drugs.”
Early Pediatric Planning Lauded
Dr. Kaplan expressed his commendation for the study sponsor, Eli Lilly and Company, recognizing their commitment to initiating a pediatric trial program early in the drug development process. “In this case, the pediatric phase 2 trial was planned and started well before the medication was approved for adults,” he said. “This approach helps reduce the substantial time lag between adult and pediatric approval for novel therapies.” He added that larger studies are needed to confirm the safety and efficacy findings from this phase 2 trial, and that a phase 3 trial is currently underway.
Disclosures
Dr. Kaplan disclosed having received royalties from UptoDate and many of his coauthors disclosed having received consulting fees, research grants, and/or other support from pharmaceutical companies. Vuijk reports grants from KNAW Ter Meulen Beurs 2025; Boute, reports grants from Stichting Sophia Kinderziekenhuis Fonds and the KICC Registry; and de Ridder reports grants from Pifzer and Pfizer Medtalk.